Feasibility of in vivo three-dimensional T*2 mapping using dicarboxy-PROXYL and CW-EPR-based single-point imaging

Abstract

Objectives The aim of this study was to demonstrate the feasibility of in vivo three-dimensional (3D) relaxation time normalT2∗ mapping of a dicarboxy-PROXYL radical using continuous-wave electron paramagnetic resonance (CW-EPR) imaging. Materials and methods Isotopically substituted dicarboxy-PROXYL radicals, 3,4-dicarboxy-2,2,5,5-tetra(2H3)methylpyrrolidin-(3,4-2H2)-(1-15N)-1-oxyl (2H,15N-DCP) and 3,4-dicarboxy-2,2,5,5-tetra(2H3)methylpyrrolidin-(3,4-2H2)-1-oxyl (2H-DCP), were used in the study. A clonogenic cell survival assay was performed with the 2H-DCP radical using squamous cell carcinoma (SCC VII) cells. The time course of EPR signal intensities of intravenously injected 2H,15N-DCP and 2H-DCP radicals were determined in tumor-bearing hind legs of mice (C3H/HeJ, male, n = 5). CW-EPR-based single-point imaging (SPI) was performed for 3D normalT2∗ mapping. Results 2H-DCP radical did not exhibit cytotoxicity at concentrations below 10 mM. The in vivo half-life of 2H,15N-DCP in tumor tissues was 24.7 ± 2.9 min (mean ± standard deviation [SD], n = 5). The in vivo time course of the EPR signal intensity of the 2H,15N-DCP radical showed a plateau of 10.2 ± 1.2 min (mean ± SD) where the EPR signal intensity remained at more than 90% of the maximum intensity. During the plateau, in vivo 3D maps with 2H,15N-DCP were obtained from tumor-bearing hind legs, with a total acquisition time of 7.5 min. Conclusion EPR signals of 2H,15N-DCP persisted long enough after bolus intravenous injection to conduct in vivo 3D normalT2∗ mapping with CW-EPR-based SPI.

Review—Quantification of Hydrogen Peroxide by Electrochemical Methods and Electron Spin Resonance Spectroscopy

“…447 Relevant advances in improving the spatio-temporal resolution and sensitivity of this technique have been described and summarized recently. [448][449][450][451] A variety of aspects have to be considered when using in-vivo ESR: (i) maintenance of physiological conditions, like pH, temperature and oxygen supply during the on-going measurement, (ii) choice of a suitable spin trap, (iii) fast acquisition of data to monitor situations in real-time, (iv) improvement of signal-to-noise ratio of the data, (v) clearly defined ("simple") ESR spectra or particular aspects of the spectra, like the amplitude, and (vi) reasonable compromise between spatial resolution and signal yield. To meet all these challenges and enable reliable in-vivo ESR measurements even for very sophisticated experimental requirements, companies have developed and specifically optimized hard-and soft-ware of ESR devices.…”

A 750-MHz electronically tunable resonator using microstrip line couplers for electron paramagnetic resonance imaging of a mouse tumor-bearing leg

“…8 confirm that the developed tunable resonator could be used for in vivo EPR imaging of a mouse tumor-bearing leg. The 2 H, 15 N-DCP imaging probe exhibits very low toxicity [34] and none of the subject mice in our experiments died. Nevertheless, the lowest possible dose of imaging agent is always preferable for animal studies.…”

“…EPR data-acquisition was started 5 minutes after the injection and a total of 3375 projections were acquired over the next 7.5 minutes. In our previous study, we showed that this acquisition scheme ensures a high intensity for the EPR signal and a steady concentration of 2 H, 15 N-DCP radical in the tumor tissue [34]. The incident RF power for imaging of a tumor-bearing mouse leg was 23 mW.…”

“…The details of animal preparation have been reported previously [34]. In brief, six-week-old C3H/HeJ male mice were purchased from Japan SLC (Hamamatsu, Japan).…”

“…Murine squamous cell carcinoma (SCC VII) cells [35] were subcutaneously injected into the right hind leg. The cells were cultured as previously reported [34]. In vivo EPR imaging of tumor-bearing mice was performed 6 days after the implantation of SCC VII cells.…”